The general goal of this work is to understand the molecular basis of carcinoma invasion. Hemidesmosomes are the molecular basis for stable attachment in most epithelial cells, because these multiprotein structures provide a firm link between the basal lamina and the cytokeratin network. Most carcinoma cells loose their hemidesmosomes. Hemidesmosomes need to be disrupted for a cell to migrate. The focus of our study is to understand how the disassembly of the hemidesmosome is regulated and what its dynamics are. We hypothesize that phosphorylation of key hemidesmosomal components is the molecular basis for regulating hemidesmosome disassembly. We will focus mostly on one of the hemidesmosome components, the integrin alpha6beta4, because this integrin is the key organizer of hemidesmosomes and it has been previously shown that it can be mobilized from hemidesmosomes using a PKC-dependent mechanism that includes serine phosphorylation of the beta4 subunit. Recent data suggest that integrin endocytosis is important for cell migration. We hypothesize PKC alpha regulates the disassembly of the hemidesmosome by regulating both the dissociation and internalization of the alpha6beta4 integrin, allowing the alpha6beta4 integrin to be transported intracellularly towards actin rich protrusions, where it functions in migration.